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Am J Physiol Heart Circ Physiol (February 3, 2006). doi:10.1152/ajpheart.01327.2005
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Submitted on December 16, 2005
Accepted on January 27, 2006

Significance of Changes in TNF-{alpha} and IL-10 levels in the progression of heart failure subsequent to Myocardial Infarction

Kuljeet Kaur1, Anita K Sharma1, and Pawan K Singal1*

1 Physiology, University of Manitoba, Winnipeg, MB, Canada

* To whom correspondence should be addressed. E-mail: psingal{at}sbrc.ca.

Objective: We tested whether a decrease in the ratio of anti-inflammatory cytokine, interleukin-10 (IL-10) and Tumor necrosis factor-{alpha} (TNF-{alpha}) correlate with the decrease in cardiac function in heart failure. Background: TNF-{alpha} is suggested to play a role in the progression of heart failure and its effect in many tissues is modulated by IL-10. Any relationship in these two cytokines in heart failure has never been examined. Methods: Coronary artery ligated rats were assessed by both echocardiographic and hemodynamic techniques for their cardiac function at 1, 4, 8 and 16 weeks post myocardial infarction (PMI). Membrane bound and soluble fractions of TNF-{alpha} and IL-10 proteins, their ratio and their mRNA were analyzed. Losartan was used to modify the function in the 4 W PMI rats to further validate the relationship between IL-10/TNF-{alpha} ratio and cardiac function. Results: Cardiac function deteriorated with time in all the PMI groups, with a severe failure seen at 16W PMI. Both the TNF-{alpha} protein fractions were increased in 1 and 4W PMI groups whereas TNF-{alpha} mRNA was increased in 4 and 8W PMI. Membrane bound IL-10 protein and mRNA were decreased in 4, 8 and 16W PMI groups. The IL-10/TNF-{alpha} protein ratio decreased in all the PMI groups and this correlated with the depressed cardiac function. Losartan improved cardiac function, both fractions of TNF-{alpha} and IL-10 proteins, their ratio and IL-10 mRNA. Conclusion: This study suggests that a decrease in the IL-10 and IL-10/TNF-{alpha} ratio correlate with the depressed cardiac function.




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